Pluto Bioinformatics

GSE146403: Loss of the nuclear protein RTF2 enhances influenza replication

Bulk RNA sequencing

While hundreds of genes are induced by Type I interferons, their roles in restricting the influenza life cycle remain mostly unknown. Using a loss-of-function CRISPR screen in cells pre-stimulated with Type I interferon, we identified a small number of factors required for restricting influenza A virus replication. In addition to the known components of the interferon signaling pathway, we found a new factor, Replication Termination Factor 2 (RTF2). RTF2 restricts influenza, at least, at the nuclear stage of the viral life cycle based on several lines of evidence. First, a deficiency in RTF2 leads to higher levels of viral primary transcription, even in the presence of cycloheximide to block genome replication and secondary transcription. Second, cells that lack RTF2 have enhanced activity of a viral reporter that depends solely on four viral proteins that carry out replication and transcription in the nucleus. Third, when RTF2 protein is mislocalized outside the nucleus, it is not able to restrict replication. Furthermore, the absence of RTF2 not only led to enhanced viral transcription but also to reduced expression of anti-viral factors in response to interferon. RTF2 thus inhibits primary influenza transcription, likely acts in the nucleus, and contributes to upregulation of antiviral effectors in response to Type I interferons SOURCE: Nir Hacohen Broad Institute of MIT and Harvard